Project Summary Most traits, including complex diseases like diabetes, psychiatric disorders and cardiovascular disease, have a strong genetic component. However, how individual alleles affect trait expression may depend on genotypes at other loci, or on aspects of the environment. The proposed research seeks to elucidate the extent and nature of conditionally functional mutations in the determination of complex traits, using the developmental and genetic model organism C. elegans. This worm is amenable to high- throughput, automated phenotyping methodologies, which permit sufficient replication to detect the potentially subtle effects of natural allelic variants. Thus, the work leverages the resources in an experimental model system to ask questions about the functional consequences of natural genetic variation. By working at the interface of quantitative and model system genetics, this research aims to improve our understanding of complex trait architecture as well as provide new insight into the genetic and developmental mechanisms that lie between genotype and phenotype.